ArticleThe Journal of biological chemistry2015
Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.Advances in experimental medicine and biology · 2026Review
- Engineering affinity-matured variants of an anti-polysialic acid monoclonal antibody with superior cytotoxicity-mediating potency.Cell chemical biology · 2025Article
- Affinity Affects the Functional Potency of Anti-GD2 Antibodies by Target-Mediated Drug Disposition.Cancers · 2025Article
- Protein Recognition of Glycosphingolipids in Membranes: Mechanistic and Quantitative Insights.Analytical chemistry · 2025Article
- Antibody Recognition of Human Epidermal Growth Factor Receptor-2 (HER2) Juxtamembrane Domain Enhances Anti-Tumor Response of Chimeric Antigen Receptor (CAR)-T Cells.Antibodies (Basel, Switzerland) · 2024Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes.Journal of hematology & oncology · 2021Article
- Article
- Tissue factor as a new target for CAR-NK cell immunotherapy of triple-negative breast cancer.Scientific reports · 2020Article
- Protein electrostatics: From computational and structural analysis to discovery of functional fingerprints and biotechnological design.Computational and structural biotechnology journal · 2020Review
- Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.Frontiers in pharmacology · 2020Review
- Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2.International journal of biological sciences · 2020Review
- Multimerization through Pegylation Improves Pharmacokinetic Properties of scFv Fragments of GD2-Specific Antibodies.Molecules (Basel, Switzerland) · 2019Article
- Novel chimeric antigen receptor T cells based on T-cell receptor-like antibodies.Blood science (Baltimore, Md.) · 2019Article
- Building Potent Chimeric Antigen Receptor T Cells With CRISPR Genome Editing.Frontiers in immunology · 2019Review
- N-terminal α-amino group modification of antibodies using a site-selective click chemistry method.mAbs · 2018Article
- Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies.Cell reports · 2017Article
- Engineered antibody CH2 domains binding to nucleolin: Isolation, characterization and improvement of aggregation.Biochemical and biophysical research communications · 2017Article
- Successful engineering of a highly potent single-chain variable-fragment (scFv) bispecific antibody to target disialoganglioside (GD2) positive tumors.Oncoimmunology · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ganglioside GD2 is highly expressed on neuroectodermal tumors and an attractive therapeutic target for antibodies that have already shown some clinical efficacy. To further improve the current antibodies, which have modest affinity, we sought to improve affinity by using a combined method of random mutagenesis and in silico assisted design to affinity-mature the anti-GD2 monoclonal antibody hu3F8. Using yeast display, mutants in the Fv with enhanced binding over the parental clone were FACS-sorted and cloned. In silico modeling identified the minimal key interacting residues involved in the important charged interactions with the sialic acid groups of GD2. Two mutations, D32H (L-CDR1) and E1K (L-FR1) altered the electrostatic surface potential of the antigen binding site, allowing for an increase in positive charge to enhance the interaction with the negatively charged GD2-pentasaccharide headgroup. Purified scFv and IgG mutant forms were then tested for antigen specificity by ELISA, for tissue specificity by immunohistochemistry, for affinity by BIACORE, for antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity in vitro, and for anti-tumor efficacy in xenografted humanized mice. The nearly 7-fold improvement in affinity of hu3F8 with a single D32H (L-CDR1) mutation translated into a ∼12-fold improvement in NK92MI-transfected CD16-mediated ADCC, a 6-fold improvement in CD32-mediated ADCC, and a 2.5-fold improvement in complement-mediated cytotoxicity while maintaining restricted normal tissue cross-reactivity and achieving substantial improvement in tumor ablation in vivo. Despite increasing GD2 affinity, the double mutation D32H (L-CDR1) and E1K (L-FR1) did not further improve anti-tumor efficacy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.